Exploring the Role of Bacterial Translation Factors in Metabolism and Stress Resistance

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Bacteria are living cells that routinely encounter stressful situations and must adapt to survive. Stresses can include acids, detergents, antibiotics, heat, too much salt, toxic metals, and the immune systems of animals that they infect. Bacterial cells can do many things to protect themselves from such stresses including detoxifying or eliminating the cause of stress or by changing some aspect of their physiology (not unlike how a human sweats when they are hot). Not all environments are equal and the way a bacterial cell survives in one environment may be detrimental in another. Bacteria have therefore evolved to link particular stress responses to cues they detect in their local environment. The details of what signals are being sensed and exactly how this information is integrated into an effective response is the focus of this research. In the previous funding cycle the Navarre lab discovered that bacteria contain a protein called “elongation factor P” or EF-P that is essential for bacterial cells to thrive under several conditions of stress like exposure to antibiotics or detergents and acid stress. During the course of this work we also observed that EF-P cells display evidence of metabolic hyperactivity. In exploring the underlying cause of this increased stress susceptibility we noted that normal Salmonella shuts down some of its metabolism (akin to hibernation) when faced with some types of stress while the strains lacking EF-P do not. A fundamental question is whether lowering metabolism renders the bacterial cell less susceptible to certain forms stress and what the consequences are if metabolism is not lowered. In the upcoming funding period we will determine exactly what parts of metabolism are different in bacterial cells lacking EF-P under normal growth and under different forms of stress. We will determine if shutting down metabolism renders the bacteria more resistant to specific types of stress and if a failure to shut down metabolism enhances their susceptibility to stress. This work will contribute to a larger body of understanding about how all living forms cope with stress, how metabolism and stress may link to aging and disease, and how metabolism can be manipulated in bacterial cells to make useful chemical products.